Science and Technology

Worldwide, cervical cancer is the second most common cause of cancer deaths in women with about a half million new cases and about a quarter of a million deaths every year. It generally occurs at younger ages, thus destroying more years of life than other female cancer, and can impair the reproductive potential of survivors. In the US, Pap smear screening and related testing have reduced the incidence of cervical cancer by 75% to about 11,000 new cases in 2007 with about 3,900 deaths.

Given the strong association between human papillomavirus (HPV) infection and cervical dysplasia and cancer, HPV plays an important etiological role in cervical carcinogenesis. However, HPV infection is common and most people eventually clear the virus without further development of carcinogenesis (See Diagram 1).

The mechanism by which HPV contributes to cancer development is attributed in large part to the actions of the HPV E6 and E7 oncogenes. These oncoproteins inactivate tumor suppressor genes that operate at key cell cycle checkpoints. E6 binds to p53, leading to genomic instability and blocking apoptosis, allowing cells with damaged DNA to replicate rather than self-destruct. E7 binds to the retinoblastoma gene product (Rb) and Rb family members, leading to induction of DNA synthesis in keratinocytes that would otherwise be terminally differentiated and non-replicating. See Diagram 2. In precancerous lesions, E6 and E7 proteins are expressed at much higher levels than found in benign lesions

The ability to detect E6E7 oncoproteins as biomarkers for high grade cervical intraepithelial neoplasia (CIN 2/3) lesions is a critical advance that would allow practitioners to:

• differentiate benign HPV infection from precancerous lesions
• identify high-grade dysplastic cells and tumor cells in cervical cells and tissues
• mimimize unnecessary colposcopies and biopsies in woman with benign HPV infection

E6E7 oncogenes are known to be integrally involved in HPV infection and transformation but historically have been difficult to isolate. Increased expression of HPV E6E7 oncoproteins indicate progression of HPV infection advancing to CIN lesions. ("Basic mechanisms of high-risk human papillomavirus-induced carcinogensis: Role of E6 and E7 proteins" Narisawa-Saito and Kiyono, Cancer Sci 2007; 98:1505-1511.)

In addition to cervical cancer, the presence of HPV DNA has been detected in tumor tissues of head and neck, anal, oral, vulva, penile, vaginal and some skin cancers. The E6E7 biomarkers we have developed are anticipated to assess risk of cancer development associated with HPV infection in multiple populations and organ sites. See The OncoHealth Solution and Publications.